The overall goal of this study is to study the physiologic and metabolic determinants of neutrophil (PMN) dysfunctions in children with leukemia and associated disorders and to attempt the correction of PMN bactericidal defects of leukemic patients with immunometabolic manipulations in vitro. Since April 1975, 88 additional patients with leukemic or recurrent infections have been studied. The PMN bactericidal defect was confirmed in half of the leukemic patients in relapse. Significant defects of phagocytosis were also demonstrated in patients with sickle-cell disease and trisomy 21. In addition, patients with trisomy 21 displayed defective PMN and monocyte chemotaxis as well as depressed monocyte phagocytosis. Opsonization and generation of chemotactic activity by serums of trisomy 21 children was defective. Incubation of PMN's with hydrocortisone resulted in a phagocytic defect of normal PMN's, without depression of the bactericidal activity. In vitro incubation studies with vincristine (5 times 10 to the minus 5th micron) abolished the chemotaxis of normal PMN's. IgG-glucose oxidase conjugates were used successfully to opsonize Staphylococcus aureus 502 A. The opsonized bacteria were then exposed to PMN's and monocytes from female carriers of chronic granulomatous disease (CGD). In the PMN's of CGD carriers, the bactericidal defect was improved by more than 50 per-cent when IgG-glucose oxidase-opsonized bacteria were used, as compared with IgG-opsonized bacteria. Under similar conditions, the bactericidal defect of CGD monocytes were completely corrected. The studies suggest that the provision of specific antibodies conjugated to glucose oxidase might provide a corrective mechanism for clinical conditions where compromised host-defense stems from defective PMN and monocyte bactericidal activity (CGD, leukemia or some severe infections). Our studies also demonstrate two additional deleterious effects of VCR and hydrocortisone on PMN functions, which may have relevance to the increased susceptibility to bacterial infections of leukemic patients treated with these 2 drugs. BIBLIOGRAPHIC REFERENCES: Humbert J.R.: Neutrophil physiology and pathology: Introduction. Semin Hematol. 12:3, 1975. Humbert J.R. Morse H, Peakman D.C.: Application des nouvelles methodes cytogenetiques a l'etude de la leucemie. Med.Hyg. 33:284, 1975.